Cannabinoid was discovered as the main active substance contained in marijuana in 1960 and found to exhibit an activity to the central nervous system (illusion, euphoria, sensory confusion of time and space) and an activity to the peripheral cell system (immunosuppressive activity, anti-inflammatory activity, analgesic activity).
After that, anandamide and 2-arachidonoylglycerol produced from phospholipid containing arachidonic acid were discovered as an endogenous cannabinoid receptor agonist. These endogenous agonists were known to exhibit an activity to the central nervous system and an activity to the peripheral cell system. It was disclosed in Non-Patent 1 that anandamide exhibits an activity to the cardiovascular system.
A cannabinoid type 1 receptor discovered in 1990 was found to distribute in the central nervous system such as the brain. Agonists to this receptor were found to suppress the release of neurotransmitters to cause central actions such as illusion or the like. A cannabinoid type 2 receptor discovered in 1993 was found to distribute in immune tissues such as the spleen or the like. Agonists to this receptor were found to suppress an activation of cells in immunocyte or phlogocyte to exhibit an immunosuppressive activity, an anti-inflammatory activity and an analgesic activity (Non-Patent 2).
It was disclosed in Non-Patent 3 that Δ9-tetrahydrocannabinol and the like exhibit bronchodilatation. Furthermore, It was disclosed in Patent 1 that a cannabinoid receptor agonism exhibits an anti-pruritus activity.
Known as compounds having a cannabinoid receptor agonistic activity are isoindolynone derivatives (Patent 2), pyrazole derivatives (Patent 3), quinolone derivatives (Patent 4 and Patent 5), pyridone derivatives (Patent 6), thiazine derivatives (Patent 7 and Patent 8), and the like.                Patent 1: WO03/035109        Patent 2: WO97/29079        Patent 3: WO98/41519        Patent 4: WO099/02499        Patent 5: WO00/40562        Patent 6: WO02/053543        Patent 7: WO01/19807        Patent 8: WO02/072562        Non-Patent 1: Hypertension (1997) 29, 1204-1210        Non-Patent 2: Nature, 1993, 365, 61-65        Non-Patent 3: Journal of Cannabis Therapeutics 2002, 2(1), 59071        